Download Head and Neck cancer: Risk factors, imaging, treatment concepts

Head and Neck cancer:
Risk factors, imaging, treatment
concepts, follow-up
Frank Zimmermann
Klinik für Strahlentherapie und Radioonkologie
Universitätsspital Basel
Petersgraben 4
CH – 4031 Basel
www.radioonkologiebasel.ch
Histopathology
Squamous cell carcinoma !
• Laryngeal cancer
• Oropharyngeal cancer
• Hypopharyngeal cancer
• Oral cancer
• Nasopharyngeal cancer (non-ceratonized)
Adeno- / Adenoidcystic carcinoma
• Tumors of nose and paranasal sinus
• Tumor of the glands
Others: Melanoma, Lymphoma, Sarcome a.o.
LN-Level
IA and IB submental / submandibular along ventral
digastricus
II A and II B
upper jugular along V. jugularis
III middle jugular between hyoid and membrana
cricothyroidea
IV lower jugular between membrana Membrana
cricothyroidea and clavicula
V A and VB
posterior cervical between M scm and
trapezius
VI anterior pretracheal between hyoid and jugulum
LN-Level
LN level and CT-based boundaries
Lymphatic spread
Nasopharyngeal
Parotid LN
Most cover from ca. 5 %
likelyhood of infiltration
Maxilla
Hard palate
ALL
Oral cavity
Oropharynx
Imaging
Techniques:
- Clinical evaluation
- Ultrasound
- Endoscopy
- CT-scan
- MRI
- (FDG)-PET
Staging
Type of imaging depending on initial stage and site
1. Laryngeal cancer vocal cord cT1
2. Nasopharyngeal cancer cT2 G3
3. Hypopharyngeal cancer cT2 cN1
T-Staging
TX
T0
Tis
T1
T2
T3
T4
primary not measurable
No primary
Carcinoma in situ
largest tumor extension < 2 cm
tumor extension 2-4cm
Largest tumor extension > 4 cm
Infiltration of neighbored structures
N-Staging
NX
N0
N1
N2a
N2b
N2c
N3
Regional LN-metastases not measurable
No regional LN-metastases
Isolated ipsilateral metastase < 3 cm
Isolated ipsilateral metastase 3-6 cm
Multiple ipsilateral metastasis < 6 cm
Bilateral / contralateral metastasis < 6cm
Metastase(n) > 6 cm
UICC-Staging
Stage
0
I
II
III
IVA
IVB
IVC
T
Tis
T1
T2
T1, T2
T3
T1, T2, T3
T4a
T4b
each T
each T
N
N0
N0
N0
N1
N0, N1
N2
N0, N1, N2
each N
N3
each N
M
M0
M0
M0
M0
M0
M0
M0
M0
M0
M1
Further characteristics
L0 vs. L1
V0 vs. V1 vs. V2
G1 vs. G2 vs. G3 vs. G4
Rx vs. R0 vs. R1 vs. R2
Treatments concepts: When for whom?
Resection
Radiation therapy
Combined radio-chemotherapy
Fractionation of radiation therapy
Beitler et al. IJROBP 2014
Results of fractionation
Pats. Fract.
Weeks
TD (Gy)
GD (Gy)
DFS
OS
268
35
7
1 x 2,0
70
31,7
46,1
263
68
7
2 x 1,2
81,6
37,6
54,5
274
42
8
2 x 1,6
67,2
33,2
46,2
268
42
6
1 x 1,8
1,8 + 1,5
72
39,3
50,9
Fu et al, Int J Rad Oncol Biol Phys 2000; Beitler et al. IJROBP 2014
Fractionation of radiation therapy
Beitler et al. IJROBP 2014
Fractionation of radiation therapy
Beitler et al. IJROBP 2014
Fractionation of radiation therapy
Beitler et al. IJROBP 2014
Only hyperfractionation superior
Beitler et al. IJROBP 2014
Radiation treatment planning
Marking of tumor resection borders improve radiation
treatment planning after free flap reconstruction in
head neck cancer surgery:
titanium clips to reduce the dose in the center of the
flap by IMRT
Bittermann et al. J Cranio-Max Fac Surg 2015
Radiochemotherapy
Standard: simultaneous RCT with Cisplatin
(2 x 5 x 20 mg/m2 or 2-3 x 100 mg/m2)
Simultaneous RCT
Significant advantage of combined simultaneous
Radiochemotherapy vs. pure radiotherapy
(British Medical Journal, Budach et al. 2006)
Radiochemotherapy (DAHANCA 18)
227 pats. with stage III / IVa HNC
RT: 66-68 Gy in 6 weeks (6 x 2 Gy/week)
CTx: 40 mg Cisplatin weekly + Nimorazole
Results: 66 % full treatment; LRC 80 %; OS 72 %
Tube feeding during RCT: 64 %, at 1-year 6 %
Bentzen et al. Acta oncol 2015
Radiochemotherapy
(DAHANCA 18)
Bentzen et al. Acta oncol 2015
Radiochemotherapy (DAHANCA 18)
Bentzen et al. Acta oncol 2015
Combined radiochemotherapy (GORTEC)
109 pats. with stage III / IVa HNC (cN2b-3):
RT: 64 Gy in 5 weeks
CTx: 3 x 100 mg Cisplatin + 2 x 5 x 1000 mg 5-FU
Vs.
RT: 64 Gy in 3 weeks
Bourhis et al. Radiother Oncol 2011
Combined radiochemotherapy (GORTEC)
Bourhis et al. Radiother Oncol 2011
Combined radiochemotherapy (GORTEC)
Bourhis et al. Radiother Oncol 2011
Combined radiochemotherapy (GORTEC)
Bourhis et al. Radiother Oncol 2011
Combined radiochemotherapy (GORTEC)
Locoregional control and distant metastases better
with RCT (p=0.005)
Significant higher toxicity
No advantage in OS / DFS (p=0.70 / 0.16)
Conclusion: clear limits of dose intesification; no
accelerated RT + CT
Bourhis et al. Radiother Oncol 2011
Combined radiochemotherapy (RTOG0522)
891 pats. with stage III / IVa HNC (site/N-stage/PS/
IMRT/PET-CT-planning):
RT: 70-72 Gy in 6 weeks
CTx: 2 x 100 mg Cisplatin +/- Cetuximab
PFS in intent-to treat: no advantage for Cetuximab
Ang et al. J Clin Oncol 2014
Ang et al. J Clin Oncol 2014
Combined radiochemotherapy (ARO-95-06)
384 pats. with stage (III) / IVa HNC
RT: 15 x 2.0 Gy + 29 x 1.4 Gy to 70.6 Gy in 6 weeks
CTx: Mitomycin C + 5-FU
vs.
RT: 8 x 2.0 Gy + 34 x 1.4 Gy to 77.6 Gy in 6.5 weeks
LRC significantly better with RCT: 38 % vs. 26 %
Budach et al. IJROBP 2015
Combined radiochemotherapy (ARO-95-06)
Budach et al. IJROBP 2015
Combination besides chemotherapy
Radiotherapy plus Cetuximab (rand.)
Improved survival with Cetuximab
(57 % vs. 44 % 3-J-OS)
Advantage: good toxicity profile (but severe dermatitis)
Disadvantage: only 1 positive, pharma-supported trial
No advantage to classical RCT
Osteonecrosis ?
Vermorken et al. 2008, Cohen et al.
Bonner et al. Proc ASCO 2005
Intra-arterial chemotherapy (RADPLAT)
237 pats. with stage III / IVa HNC
RT: 70 Gy in 7 weeks
CTx: 4 x 150 mg Cisplatin i.a.
Vs.
CTx: 3 x 100 mg Cisplatin i.v.
LRC not better with RCT: 60 % vs. 50 %
Heukelom et al. Head Neck 2015
Intra-arterial chemotherapy (RADPLAT)
Heukelom et al. Head Neck 2015
Laryngeal cancer
T1a-tumors:
Transoral laser surgery vs. radiotherapy
-
Similar local control rate
-
Similar voice quality
-
Higher laryngeal preservation with initial limited
surgery
Abdurehim et al. Head Neck 2010
Laryngeal cancer
Abdurehim et al. Head Neck 2010
Laryngeal cancer: Overall survival
Abdurehim et al. Head Neck 2010
Laryngeal cancer: Local control
Abdurehim et al. Head Neck 2010
Laryngeal cancer: Larynx preservation
Abdurehim et al. Head Neck 2010
Laryngeal cancer: Phonation time
Abdurehim et al. Head Neck 2010
Laryngeal cancer
T1-2-tumors:
Transoral laser surgery vs. radiotherapy
-
Similar local control rate
-
Similar voice quality
-
Similar larynx preservation
-
No advantage for either therapy
Feng et al. Head Neck 2010
Laryngeal cancer: treatment of cN0-neck
Retrospective trials on 792 pats:
- Neck dissection
- Neck radiation
- Neck dissection and radiation
- Wait and see
No significant difference in OS / DFS !
Goudakos et al. EJSO 2009
Laryngeal cancer
Man, born 1939, with coronar heart disease, cardial
insufficiency NYHA II, COPD Gold II, Diabetes IIb,
100 py
Laryngeal carcinoma left vocal cord, cT2 cN0 cM0
G2, infiltrating into the supraglottis and into the sinus
piriformis, infiltration of paraglottic tissue, no vocal
cord fixation
Laryngeal cancer
Laryngeal cancer
Laryngeal cancer
Laryngeal cancer
Laryngeal cancer
Laryngeal cancer
Laryngeal cancer
Laryngeal cancer
Man, born 1961, 60 py, alcohol abuse
Advanced glottic cancer, pT4 pN2c (2/66) ECE, cM0,
L0, V0, R0, Stage IVA
After laryngectomy, bilateral Neck dissection, Provox
Vega 8 mm
Laryngeal cancer
Laryngeal cancer
Laryngeal cancer
Laryngeal cancer
Laryngeal cancer
Laryngeal cancer
Oral cancer
5 % of all cancer
95 % squamous cell carcinoma
Risk factors: nicotin abuse and alcohol (6-fold,
together 30-fold), for lip cancer contact with cigarette,
HPV 16
Positive factors: nutrition (lemon, vegetables, oil of
olives and fish)
Precancerous: squamous intraepithelial neoplasia
(SIN) (grade 1-3)
Oral cancer: symptoms and prognosis
Symptoms: white or red spots; ulceration; mucosal
defect; pain; difficulties during speeking; thumbness
of tongue, teeth, lips; bleeding; cervical or oral tumor;
foetor
Prognosis:
- Margin < 1 mm
- Basaloide/spindle cell tumors
- Non continuous tumor spread
Oral cancer: first steps
Screening by dentists, but not systematically (Kujan et al.
Cochrane 2003)
Prevention: information of patients (Humphris et al. Oral Oncol 2001)
Diagnostic:
- Early diagnostic improves prognosis (Pitiphat et al. J Dental Res
2002)
- Inspection (for all mucosal alterations for more
than 2 weeks)
Oral cancer: Imaging
- CT-scan or MRI (67-69;94) (before biopsy) (with
suspected metall artefacts MRI) (Van Cann et al. Int J Oral Max
Surg 2008)
- Panorama scan of mandibula
- Value of FDG-PET-CT only for LN-staging (Kim et al.
Eur J Surg Oncol 2008)
- Ultrasound and LN-staging improved by fineneedle-biopsy (Takes et al. IJROBP 1998)
- In stage III/IVa: CT-scan of thorax (US of liver)
Oral cancer: therapy
- Early stages: resection: 3 mm margins and
preservation of contuinity of mandibula (when no
infiltration of bone) (Sutton et al. Int J Oral Max Surg 2003; Wolff et al. J
Craniomax Surg 2004)
- Advanced stages: resection plus adjuvant
radiotherapy/radiochemotherapy or definitive
radiochemotherapy (Soo et al. Br J Cancer 2005) (risk of
osteonecrosis)
- Nutritional support
- Dental support
Oral cancer: therapy
- Neck dissection of level I-III (~ 30 % subclinical
metastasis) (elective – radical dissection)
- In cN+ selective ND Level I-IV (skip lesions),
sometimes modified radical ND
- Adjuvant RT / RCT in cN2a or cN2b (Vikram et al. Head Neck
Surg 1984; Bernier et al. N Engl J Med 2004)
- Salvage ND reasonable but results poor (Mabanta et al. Head
Neck 1999)
- No superiority of brachytherapy
- RCT with Cisplatin
Oral cancer: therapy
- Pure RT hyperfractionated
- No superiority of additional brachytherapy
- RCT with Cisplatin, not with Cetuximab
- Adjuvant RT / RCT in pT3-4, R1, close margins,
perinueral infiltration, vascular invasion, pN2 with
54-66 Gy
- Whole treatment within 11 weeks
Oral cancer: therapy
- Pure RT hyperfractionated
- No superiority of additional brachytherapy
- RCT with Cisplatin, not with Cetuximab
- Adjuvant RT / RCT in pT3-4, R1, close margins,
perinueral infiltration, vascular invasion, pN2 with
54-66 Gy
- Whole treatment within 11 weeks
Oropharyngeal cancer
105 pats., stage III/IV oropharyngeal cancer
RCT: 65-70 Gy, sim. Cisplatin (35 mg/sqm weekly)
Rand. 2-3 cycles neoadjuvant Cisplatin (75mg/sqm) /
5-FU (3x800 mg/sqm)
Results: Improved 2-years DFS with neoadjuvant CTx
But: high drop-out rate in experimental arm (35 %)
Gupta et al. Cancer Biol Ther 2009
Oropharyngeal cancer
Gupta et al. Cancer Biol Ther 2009
Oropharyngeal cancer
Gupta et al. Cancer Biol Ther 2009
Oropharynxkarzinom: shortened RT-time?
Normal: ~ 45 % 5-y-overall survival with 76 Gy
Local recurrence problem No. 1
Is increasing aggressiveness with shorter
overall treatment time feasible ?
Hyperfractionated-accelerated RT: 2 x 1,6 Gy to
64 Gy in stage III and IVA: 65 % 5-y-OS
Waldron et al. Radiother Oncol 2008
HPV-status
Important in oropharyngeal cancer, increasing in other
sites
5-20 % of all HNC, 40-90 % of oropharyngeal
HPV-16, but different staining and definition
Middle-aged, white men; non-smokers; non- to
moderate-drinkers; higher socioeconomic status; better
performance status
Boscolo-Rizzo et al. Acta otorhinlaryngol ital 2013; Larsen et al. BJC 2014
HPV-status
Lower T- but higher N-status; non-keratinizing; poorly
differentiated
Better treatment response and better modalityindependent outcome
So far no de-escalation in treatment !
Boscolo-Rizzo et al. Acta otorhinlaryngol ital 2013
Hypopharyngeal cancer
Nasopharyngeal cancer
Risk factors:
latent Epstein-Barr-Virus infection (IgA and IgG;
EBV-DNA)
Chemicals (i.e. salted dried fish)
Genetic disposition (Deletion chromosom 3p and 9p;
HLA-Antigen A2, B17, Bw46)
Chan Teo; Tsao
Nasopharyngeal cancer
Symptoms:
Bleeding
Serotympanon (Tuba Eustachii)
Breathing through nose hindered
Loss of smell sensation
Pain
Enlarged LN (> 60 %)
Lee et al 2014
Nasopharyngeal cancer
Risk factors:
latent Epstein-Barr-Virus infection (IgA and IgG;
EBV-DNA)
Chemicals (i.e. salted dried fish)
Genetic disposition (Deletion chromosom 3p and 9p;
HLA-Antigen A2, B17, Bw46)
Nasopharyngeal cancer
Staging:
Inspection, palpation (LN)
Panendoscopy (with biopsy – CUP)
MRI, if suspecious for infiltration CT-scan, too
Sonography of LN
X-ray lung / CT-scan /FDG-PET-CT-scan
NCCN 2014; Ng Chan 2008
Nasopharyngeal cancer
Treatment:
cT1-2 cN0-1: RT or RCT (simultaneous or sequential)
cT3-4 or cN 2: simultaneous RCT (CisplatinM
Oxaliplatin)
NCCN 2014; Baujat et al.; Zhang Zhao et al.
IMRT in nasoparyngeal cancer
Significant improvement of Xerostomia (CTC °II)
64 %
- After 3 Months:
2,5 %
- After 24 Months:
IMRT vs. conventional planning
- After 24 Months:
12 % vs. 67 % Xerostomia > °I
No increased recurrence rate
Chao et al. 2003; Lee et al. 2006;
Liu et al. 2006; Wolden et al. 2006
Nasopharyngeal cancer
Treatment:
IMRT 70-74 Gy, 5 x 2 Gy per week; Cisplatin 100 mg/m2
day 1, 22, 43; and up to 3 cycles Cisplatin 80 mg/m2 and
5-FU 4 x 1000 mg/m2
IMRT 70-74 Gy, 5 x 2 Gy per week; Cisplatin 40 mg/m2
day 1, 8, 15, 22, 29, 36
NCCN 2014; Baujat et al.; Zhang Zhao et al.
Postop. radiochemotherapy
2 randomized trials
Indication for simultaneous combined RCT:
- T3-4 R1
- ECE in LN
Concept: up to 64 Gy plus Cisplatin
Postop. radiochemotherapy (RTOG 0234)
238 pats., stage III-IVa, with R1/ECE,>2LN+
RT: 60 Gy
CTx: Cetuximab + Cisplatin 30 mg or Taxol 15 mg
2-y-OS: Cis 69 % vs. 79 % Tax (better than with
RTOG 9501 Cis-RT)
Conclusion: phase-II/III trial ongoing, not standard !
Harari et al. J Clin Oncol 2014
Follow-up
Clinically: inspection, palpation (oral, LN), compliance
Imaging: none proven superior (respect financial
aspects)
Endoscopy: to detect early secondary cancer
Schedule: 1. year – 3-monthly
2. year – 6-monthly
3.-5. year – 1-yearly
Treatment planning
Management of contralateral N0 neck
Pyriform sinus: only in N+ ipsilateral or tumor accross
the midline
Oral cavity: only in N+ ipsilateral or tumor accross the
midline or pT3
Koo et al. Laryngosope 2006; Koo et al. Head Neck 2006
Intensity modulated radiotherapy
Intensity modulated radiotherapy
Intensity modulated radiotherapy
Randomized: IMRT vs. 3-D-CRT
Trials on head neck or nasopharyngeal cancer
Toxicity RTOG>°1 or local control
All in favor of IMRT
Less xerostomia with IMRT
Same or better tumor control rates
IMRT superior !
Gupta et al. Radiother Oncol 2012; Peng et al. Radiother Oncol 2012
Randomized: IMRT vs. 3-D-CRT
Gupta et al. Radiother Oncol 2012
Proven advantage of IMRT
IMRT reasonable
Higher quality of life
No increased recurrence rates
Less than 2 % recurrences at the PTV-margin
High demand on quality assurance
Variation of GTV-definition in 14 pats.
Anderson et al. J Radiat Oncol 2014
Variation of GTV-definition
Anderson et al. J Radiat Oncol 2014
Radiation treatment planning
Bittermann et al. J Cranio-Max Fac Surg 2015
Tomotherapy
• Combination of MV-CT and
Linear accelerator
• 85 cm Gantry-opening
• Treatment volumen
diameter up to 40cm
length up to 160cm
• 6 MV Photons
• Megavolt CT (3MV)
• Proven efficious in head and
neck cancer with good dose
distribution
Tomotherapy
Spiral irradiation
Precise axial table movement
Pitch 0.0 – 1.0
Protontherapy at PSI
Web-Seite in
Internet
Technique and physics of radiation
Dose depth curves of proton
Adenoidcystic carcinoma
Primary: tongue
Recurrence (6 y.):
base of skull
Problem with
variabel dense
tissues
Perineural invasion with centripetal spread and recurrences
Protontherapy
Adenoid-zystisches carcinoma of the lacrimal gland
(from Massachusetts General Hospital)
Dose distribution of Carbon-Ions
Schulz-Ertner et al., 2003
Dose distribution of Carbon-Ions
Schulz-Ertner et al., 2003
Neutron therapy Garching
Web-Seite im Internet
Neutron therapy Garching
Neutron therapy Garching
Advantages in radiation biology: independent of
oxygenation, more double-strand breaks
Indication: glandular adenoid-cystic carcinoma
Side effects
Acute Mucositis
Likelyhood of side effects
Acute side effects
- Mucositis
- Severe Mucositis
- Dysgeusia
- Xerostomia
- Dermatitis
100 %
> 50 %
up to 100 %
bis 100 %
bis 100 %
Late side effects:
- Xerostomia
- Osteonecrosis
- Dental loss
- Dysgeusia
> 50 %
up to 10 %
up to 50 %
up to 100 %
No protection
Vitamins
Growth factors (GSF, Epo)
Selen
Misteltoe
Lambin et al., Cochrane 2009
Dental defects
Walker et al., 2011
Caries and Osteomyelitis
Causes of osteonecrosis
Insufficient compliance of the patient
- deficient oral hygiene
- inadequate use of fluor support
- pre-damaged teeth
- soft diet with high carbohydrate contents
Direct teeth damage by irradiation
Indirect teeth damage by caries
- Xerostomia
- Alteation of oral microflora
- more azidogene / cariogene bacteries
In > 50 % dentogene, trauma-induced causes for
contaminated osteonecrosis
Explanation for osteonecrosis
Care of clinically asymptomatic bone:
- No consequent care by dentists before and
after radiotherapy
- Insufficient experience in care of radiationaltered mandibulae
- Inadequate therapy at teeth extraction
Prophylaxis of radiation sequelae
• Avoid alcohol, nicotine, hot food
• Before radiation: dental preparation, (caries,
filling, pouches)
• Fluor support under prosthesis (10-30 min. per
day, break during RT)
• During radiation: intensification of oral hygiene
(to clean the mouth with water, tee, NaClsolution)
• Benzydamin (Tantum) prophylactic, compliance
problematic
• Avoid weight loss (PEG, PORT)
Prophylaxis of radiation sequelae
• Xerostomia prophylaxis: IMRT, stimulation of
saliva (z.B. oral gum, liquids), consider
Amifostine in pure radiation therapy
• Avoid definite prosthesis during RT and for
further 6 months
• Dental prosthesis during RT
• Soormucositis: top. antimykosis
• evtl. antibiotics
• Analgesics: according to WHO-schedule
Supportive care
Antioxidant with calendula officinalis: randomized
trial with less mucositis
Low-level laser: randomized trial with no benefit
Babaee et al. J Pharmaceut Sciences 2013; De Lima IJROBP 2012
With optimal care (273/639)
Complications
Percent
No complications
77.5%
Radiogen induced caries
19%
Extractions after RT
8%
Candidosis
3.5%
Radiogen induced osteonecrosis
3%
Risk factor: multimodal therapy !
Therapy of osteonekrose/xerostomia
• In severe late reactions: HBO ?
• In xerostomia: try pilocarpin when some
function of glandulae exists; oral liquids
• No artificial saliva support with products of
cellulose (more caries)
• Logopedie, swallowing training
Therapy of soft tissue/bone necrosis
• Chronic soft tissue necrosis: Pentoxifyllin
(Trental), Vitamine E
• Evtl. OP, evtl. HBO
• Test with Bisphosphonates (Take care:
mandibular necrosis !)
Conclusion
Modern tchniques allow higher dosis, but this is
not allways necessary
Perfect coordination of multimodal therapy and
supportive treatments
Critical considerations:
Indication / aim of treatment ?
What is acchievable ?
Resourcen vs. Waiting time
Treament of tumor recurrenes
Locoregional failure in more than 50 %
Re-treatment
Chemotherapy (Cisplatin/5-FU, Carboplatin/5FU,
MTX, Cisplatin/Taxol, Cisplatin/Cetuximab,
Docetaxel/Gefintib): 5 – 10 months med. surv.
Radiotherapy/Radiochemotherapy (50-65 Gy; ): 6 –
27.6 months med. surv.
Resection plus RT/RCT: curative option !
Cacicedo et al. Cancer Treat Rev 2014
Re-treatment: recommendations
No severe sequelae in previous radiation treatments
and no significant comorbidities
PET-CT for staging
Whenever feasible initial surgery and doses > 60 Gy
Re-irradiation beyond 6 months after initial treatment
Tumors < 30 cm3
GTV plus margin
IMRT or SBRT
Cacicedo et al. Cancer Treat Rev 2014
Stereotactic radiotherapy
Fixation with
- mask
Navigation with
- frame
- pure imaging
Nasopharynx
Med. FU 20,3 months; 5,7 (0,8-24,7) ml
Pat., after RCT
Dose
34 < 6 Months
3 x 6 Gy
56 > 6 Months
6 x 8 Gy
Wu et al. IJROBP 2007
Nasopharynx
Pat., after RCT
34 < 6 Months
56 > 6 Months
Dose
3 x 6 Gy
6 x 8 Gy
CR
66 %
63 %
3-JPFS
72,3 %
42,9 %
3-JLRSur
89,4 %
75,1 %
17 pats. complications: 6 mucosa-necrosis, 2 deadly bleeding;
9 brain necrosis, 0 deadly
Wu et al. IJROBP 2007
Head neck cancer
Pats.: 18 resp. 14; med. FU 30,4 vs. 25,6 for liv.
RT: only GTV; 28 x 1,8 Gy vs. 6 x 6 Gy;
CTx: Cetuximab 400/250 mg/m2
Balermpas et al. IJROBP 2012; Comet et al. IJROBP 2012
Head Neck Cancer
PFS 7,3 vs. 8,8 Months; 47 % vs. 75 % Remission
5 Dermatitis °III, 5 Trismus °III vs. 2 Dermatitis °III
Balermpas et al. IJROBP 2012; Comet et al. IJROBP 2012
Concepts and Dosis
•
•
•
•
•
Curative vs. palliative
Large vs. small target volume
20-75 Gy total dose
1,2-6,0 Gy single dose
Defintive, postoperative or simultaneous
with chemotherapy
Palliative radiotherapy
Palliative:
2 x 6,0 Gy / pro week
to 30 Gy TD
4 x 3,5 Gy / 2 days, each
month to 42 Gy TD
Results:
80 % Remission
> 60 % symptom improvement
Median survival 6 months
2-year survival ca. 15 %
Low risk of osteonecrosis !
Radiotherapy in NHL
Definitive curative radiotherapy
24 – 40 Gy
- Total dose:
- Local control:
> 90 %
33-72 %
- 10-year recurrence free:
Pure palliative radiation therapy:
- Total dose:
4,0 Gy
- Remission rate:
> 80 %
- Local control:
> 50 %
Low risk of osteonecrosis !
Tumors at the base of skull
Fixation with
- Frame
- Mask
Adenoidcystic carcinoma
Adenoid-cystic carcinoma with invasion of the base of skull
5-jahres Tumorkontrolle (%)
Protonen:
100
Pommier et al.
MGH, 2006
80
Kohlenstoff-Ionen
60
Neutronen
40
Photonen
20
20
40
60
80
Dosis [ Gy (RBE)]
100
Results of protontherapy
Paul Scherrer Institute:
Tu-control
5 years
Chordoma
81 %
Chondrosarcoma
94 %
0.2
0.4
0.6
0.8
1.0
Time
to control
local failure
Local
Chordoma
Chondrosarcoma
0.0
P=0.25
0
20
40
60
80
months
Severe toxicity: 5 – 7 %
Mass. General Hospital:
Tu-control
5 years
Chordoma
73 %
Chondrosarcoma
98 %
Chordoma before and after Carbon-Ions
Schulz-Ertner et al., 2003
Chordoma of the skull base
5-years tumor control (%)
Photons
small chordoma
chondrosarcoma
100
Romero 1993
Zorlu 2000
Debus 2000
80
Protons
60
Munzenrider 1999
Ares 2007
Hug 1999
40
C-Ions
20
Schulz-Ertner
20
40
60
80
Dose [ Gy (RBE)]
100
Results of Carbon-Ions-therapy
Chordoma and chondrosarcoma of skull base
Schulz-Ertner et al., 2003
Phase-II trials
236 pats., 16 x 4 Gy or 16 x 3,6
5-y. loc.reg. control
Melanoma
Adenoidcyst. Ca.
Adenocarcinoma
SC-Ca.
Sarcoma
75 %
73 %
73 %
61 %
24 %
Late side effects
Grade II mucositis
Grade II dermatitis
2%
3%
Mizoe et al. 2012
Chordoma-/Chondrosarcoma-Therapy
Pharyngeal tumors
In total 4 trials with 531 pats. neutrons vs. photons
and 1 trial with 327 pats. neutrons plus photons vs. photons:
No significant difference
Cochrane database 2010, Griffin et al. 1984, MacDougall et al.
1990, Maor et al. 1986, Maor et al. 1995, Griffin et al. 1989)
Summary: concepts
Definitive radiochemotherapy: simultaneous
Cisplatinum-based
If contra-ind.: Cetuximab or Mito/5-FU or else
Radiation therapy alone:
in stage I: conventional fractionation
in stage III-IVa: altered fractionation
Postoperative radiochemotherapy: R1 or ECE
Larynx preservation: concept open (neoadj. CTx vs. RCT)
Summary: techniques
In squamous cell carcinoma: IMRT (Linac or
tomotherapy)
Different techniques: in selected cases only
In adenoidcystic carcinoma: Neutrons or protons
In chordoma / chondrosarcoma: protons / ions
In early stage oral cancer: brachytherapy
For tumor recurrences: consider hypofractionated
schedules in palliation and aggressive retreatment in
curative options